Methyl iodide → 1-Methylpiperidine-4-carboxylic acid

A mixture of ethyl piperidine-4-carboxylate (4.72 g), methyl iodide (2.24 mL), potassium carbonate (8.29 g) and acetonitrile (50 mL) was stirred at room temperature for 2 hrs. The reaction mixture was concentrated under reduced pressure and water (150 mL) was added. The mixture was extracted with ethyl acetate (150 mL). The ethyl acetate layer was washed with saturated brine (100 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. A 1N aqueous sodium hydroxide solution (20 mL) was added to the residue (2.64 g), and the mixture was stirred overnight at room temperature. The reaction mixture was neutralized by adding 1N hydrochloric acid (20 mL) and the mixture was concentrated under reduced pressure. Ethanol was added to the residue, and the precipitate was filtered off. The filtrate was concentrated under reduced pressure. This step was repeated and ethanol and ethyl acetate were added to the residue for crystallization to give 1-methylpiperidine-4-carboxylic acid (1.79 g) as a colorless solid.

1. concentrationThe reaction mixture was concentrated under reduced pressure and water (150 mL)
2. additionwas added
3. extractionThe mixture was extracted with ethyl acetate (150 mL)
4. washThe ethyl acetate layer was washed with saturated brine (100 mL)
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. additionA 1N aqueous sodium hydroxide solution (20 mL) was added to the residue (2.64 g)
8. stirringthe mixture was stirred overnight at room temperature
9. additionby adding 1N hydrochloric acid (20 mL)
10. concentrationthe mixture was concentrated under reduced pressure
11. additionEthanol was added to the residue
12. filtrationthe precipitate was filtered off
13. concentrationThe filtrate was concentrated under reduced pressure
14. additionethanol and ethyl acetate were added to the residue for crystallization

ORD record

ord-8628492bd7d04249a2bfaba6ab3bcc92

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08980322B2